Low-density lipoprotein (LDL) receptors are the major cholesterol-carrying
lipoproteins of plasma. Seven successive cysteine-rich repeats of about 40
amino acids are present in the N-terminal of this multidomain membrane protein
[1]. Similar domains have been found (see references in [2]) in other
extracellular and membrane proteins which are listed below:

Complement factor I, which is responsible for cleaving the α-chains of
C4b and C3b. It consists of a FIMAC domain (Factor I/MAC proteins C6/C7), a
scavenger receptor-like domain, 2 copies of LDLRA and a C-terminal serine
protease domain.

Complement components C6, C7, C8 and C9. They contain each one LDLRA
domain.

Vertebrate enterokinase (EC 3.4.21.9), a type II membrane protein of the
intestinal brush border, which activates trypsinogen. It consists at least
of a catalytic light chain and a multidomain heavy chain which has 2 LDLRA,
a MAM domain (see <PDOC00604>), a SRCR domain (see <PDOC00348>) and a CUB
domain (see <PDOC00908>).

Human autosomal dominant polycystic kidney disease protein 1 (PKD1), which
is involved in adhesive protein-protein and protein-carbohydrate
interactions. The potential calcium-binding site of its single LDLRA domain
is missing.

Drosophila serine protease nudel (EC 3.4.21.-), which is involved in the
induction of dorsoventral polarity of the embryo. It has 11 LDLRA domains,
3 of which miss the first disulfide bond (C1-C3).

Avian subgroup A rous sarcoma virus receptor (1 copy of LDLRA).

Bovine Sco-spondin, which is secreted by the subcommissural organ in
embryos and is involved in the modulation of neuronal aggregation. It
contains at least 2 EGF-like domains and 3 LDLRA domains.

The LDL-receptor class A domain contains 6 disulfide-bound cysteines [4] and a
highly conserved cluster of negatively charged amino acids, of which many are
clustered on one face of the module [2]. A schematic representation of this
domain is shown here:

'C': conserved cysteine involved in a disulfide bond.
'x': any residue.
'*': position of the pattern.

In LDL-receptors the class A domains form the binding site for LDL [1] and
calcium [5]. The acidic residues between the fourth and sixth cysteines are
important for high-affinity binding of positively charged sequences in LDLR's
ligands [6]. The repeat has been shown [2] to consist of a β-hairpin
structure followed by a series of β turns. The binding of calcium seems to
induce no significant conformational change.

Last update:

April 2006 / Pattern revised.

Technical section

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